image: Weight-loss response groups defined by maximum weight loss in two-year follow up period.
Credit: Venkatakrishnan et al.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become massively popular for weight loss, but results vary from person to person and drug to drug. Venky Soundararajan and colleagues explore the full range of responses to tirzepatide (e.g., Mounjaro or Zepbound) and semaglutide (e.g.,Ozempic, Wegovy, or Rybelsus) by analyzing de-identified electronic health records for matched cohorts of 10,339 tirzepatide-treated and 10,339 semaglutide-treated patients. In the real world, outcomes ranged from minimal weight loss to more than 25% reduction in body weight. Patients taking tirzepatide lost more weight than those taking semaglutide (mean reduction, 14.7% vs. 10.8% of body weight). The tirzepatide group had nearly twice as many “high responders,” defined as people who lost more than 15% of their body weight in a year, as the semaglutide group. Tirzepatide patients also had fewer gastrointestinal, headache, and fatigue adverse events than semaglutide patients. Female and white patients on either drug more frequently achieved significant weight loss than male, black, and Hispanic patients, who were more likely to lose less than 5% of their body weight in a year. According to the authors, the reasons for these demographic patterns are unknown and should be investigated.
Journal
PNAS Nexus
Article Title
Weight-loss dynamics with tirzepatide versus semaglutide
Article Publication Date
16-Jun-2026
COI Statement
The authors are employees of nference, Inc., which conducts research collaborations with various biopharmaceutical companies, including Eli Lilly and Company and Novo Nordisk A/S, whose GLP-1 receptor agonist products (tirzepatide and semaglutide) are included in this study. None of these companies, nor any other nference collaborator, funded, supported, or had any role in the independent study design, data acquisition, analysis, interpretation, manuscript preparation, or the decision to submit this work for publication. All analyses were conducted by the authors using de-identified electronic health record data. The authors declare no additional competing interests.